A Double-Blind, Placebo Controlled Study of Intravenous Immunoglobulin for HIV-Associated Myelopathy

• ClinicalTrials.gov Identifier: NCT01561755
• Recruitment Status: Terminated
• First Posted: March 23, 2012
• Results First Posted: April 13, 2018
• Last Update Posted: April 13, 2018
• Sponsor: David M. Simpson
• Collaborator: CSL Behring
• Information provided by (Responsible Party): David M. Simpson, Icahn School of Medicine at Mount Sinai

Study Description

Brief Summary:

The purpose of this study is to determine whether Intravenous Immunoglobulin (IVIG) is an effective treatment for HIV associated myelopathy.

Condition or disease	Intervention/treatment	Phase
HIV-associated Myelopathy	Drug: Intravenous Immunoglobulin; Drug: Placebo	Phase 4

Detailed Description:

The purpose of this study is to determine whether or not intravenous immunoglobulin (lVlg), brand name Privigen, is effective in treating a disorder called HIV-associated myelopathy (HIVM). This drug is currently not approved by the Food and Drug Administration (FDA) for treating this disorder.

HIVM is a spinal cord disease that occurs at any stage of HIV infection. It is not known what causes this condition, but symptoms can include weakness in the lower body and problems with frequent urination or problems with bowel function, trouble walking or performing sexually.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo Controlled Study of Intravenous Immunoglobulin for HIV-Associated Myelopathy
• Study Start Date: February 2012
• Actual Primary Completion Date: September 2016
• Actual Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intravenous Immunoglobulin; Intravenous Immunoglobulin - 2gr/kg over 2 days of Privigen®	Drug: Intravenous Immunoglobulin; Intravenous Immunoglobulin - 2gr/kg over 2 days of Privigen®; Other Names: Privigen®; IVIG
Placebo Comparator: Placebo; Saline 2gr/kg over 2 days of saline	Drug: Placebo; Placebo - 2gr/kg over 2 days of saline; Other Name: Saline

Outcome Measures

Primary Outcome Measures :

1. Strength Scores [ Time Frame: at 2 months ]
   Strength score as measured by pounds of force sustained in lower extremity strength.

Secondary Outcome Measures :

1. Walking Test [ Time Frame: at 2 months ]
   2 minute walking test
2. Urinary Function [ Time Frame: 2 months ]
   0 = Normal bladder function, 1 = Asymptomatic on current treatment, 2 = Urinary frequency, hesitancy, urgency, with no incontinence, 3 = Occasional urinary incontinence (once or more during the last month but not every week) or intermittent catheterization, 4 = Frequent urinary incontinence, or occasional incontinence despite regular catheterization, 5 = Daily urinary incontinence or permanent catheter
3. Bowel Function [ Time Frame: 2 months ]
   0 = No bowel problems, 1 = Asymptomatic on current drug tx or constipation not requiring any tx, 2 = Constipation requiring laxative or suppositories or fecal urgency, 3 = Constipation requiring the use of an enema, 4 = Constipation requiring manual evacuation of stools or occasional fecal incontinence (once or more during the last month but not every week, 5 = Weekly fecal incontinence
4. Hughes Function Score [ Time Frame: at 2 months ]
   0 = Normal strength; 1 = minor symptoms but capable of running; 2 = The subject is able to walk 30 ft. but unable to run; 3 = The subject is able to walk 30 ft. with the assistance of one person; 4 = A walker or cane; 5 = The subject is unable to walk.
5. Impression of Change Score - Participant [ Time Frame: at 2 months ]
   The self-report measure Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of treatment 1. Marked improvement; 2 Moderate Improvement; 3 Minimal Improvement; 4 No Change; 5 Minimal Worsening; 6 Moderate Worsening; 7 Marked worsening
6. Impression of Change Score - Clinician [ Time Frame: at 2 months ]
   The clinician measure of Global Impression of Change reflects the clinician's view about the efficacy of treatment as measured by 1. Marked improvement; 2 Moderate Improvement; 3 Minimal Improvement; 4 No Change; 5 Minimal Worsening; 6 Moderate Worsening; 7 Marked worsening

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Documented history of HIV infection.
• Age ≥ 18
• Males and females are eligible. Subjects must agree to practice birth control or abstinence. Females of child-bearing potential must have a negative urine pregnancy within 14 days prior to study entry.
• Adequate baseline organ function including the following laboratory values within 14 days prior to study entry:
• Adequate liver function with ALT, AST and alkaline phosphatase ≤ 5 times upper limit of normal (ULN).
• Total bilirubin ≤ 2.5 mg/dL Creatinine < 2.3 Serum vitamin B12 level ≥ 200 pg/ml
• Diagnosis of HIVM by a neurologist - defined as:
• - Presence of at least two of the following symptoms:
• - Paresthesias and/or numbness in the lower extremities or in all four limbs; Weakness of the limbs, with predominance in the lower extremities; Unsteady, stiff or uncoordinated gait; Sensation of electrical shock through the back or the legs upon flexion of the neck (L'Hermitte's sign); Stiffness or spasm in the lower extremities; Urinary frequency, urgency, incontinence or retention; Fecal incontinence or retention; Sexual dysfunction with erectile impairment in men;
• - Presence of at least two of the following neurologic signs:
• - Reduction in vibratory or position sensation in the lower extremities; Hyperactive deep tendon reflexes; Abnormal response to plantar stimulation (Babinski sign); Presence of L'Hermitte sign (electrical-type sensation down the back, provoked by flexion of the neck); Weakness in the lower extremities or in all four limbs; Spastic or ataxic gait
• Antiretroviral regimen stable 2 months prior to the entry of the study.

Exclusion Criteria:

• Presence of acute, active, opportunistic infection, except oral thrush, orogenital or rectal herpes and MAI bacteremia within 2 weeks before randomization.
• Evidence of another contributing cause for myelopathy.
• Women who are pregnant, breast-feeding or planning a pregnancy.
• Active abuse of drugs or alcohol, which in the opinion of the investigator would interfere with the subject's ability to comply with the protocol.
• Any neurologic or systemic conditions, which in the opinion of the investigator would interfere with the evaluation of the subject.
• Presence of significant cardiac, pulmonary or renal disease that would place the subject at risk for the fluid and protein load of IVIg.
• History of hypersensitivity to immunoglobulin, or IgA deficiency; Vaccination with live viruses within the past 90 days; Patients receiving IVIg or other immunomodulatory agent (cyclosphosphamide, azathioprine, corticosteroids, tacrolimus, cyclosporine, OKT3, plasma exchange, alpha, beta or gamma interferon) within the past 3 months.
• Patients in whom muscle dynamometry can not be performed for any reason.

Contacts and Locations

Locations

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Sponsors and Collaborators

David M. Simpson

CSL Behring

Investigators

• Principal Investigator: David Simpson, MD; Icahn School of Medicine at Mount Sinai

More Information

• Responsible Party: David M. Simpson, Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01561755
• Other Study ID Numbers: GCO 10-1108; HS#: 11-02029
• First Posted: March 23, 2012
• Results First Posted: April 13, 2018
• Last Update Posted: April 13, 2018
• Last Verified: April 2018

Keywords provided by David M. Simpson, Icahn School of Medicine at Mount Sinai:

HIV associated myelopathy

Additional relevant MeSH terms:

Spinal Cord Diseases; Bone Marrow Diseases; Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin; Immunologic Factors; Physiological Effects of Drugs